Culture model of human corneal epithelium for prediction of ocular drug absorption.

PURPOSE: The main purpose of this study was to develop a cell culture model of immortalized epithelium from the human cornea for drug permeability testing. METHODS: Immortalized human corneal epithelial (HCE) cells were grown on filters, with various filter materials and coating procedures. In the optimal case, HCE cells were grown on polyester filters coated with rat tail collagen gel containing fibroblast cells. Transepithelial electrical resistance (TER) was measured during the growth of the cells to evaluate the epithelial differentiation and tightness of the epithelial cell layers. Transmission electron microscopy (TEM) was used to show the formation of tight junctions, desmosomes, and microvilli. Cellular morphology was characterized by light microscopy. Permeabilities of (3)H-mannitol and 6-carboxyfluorescein were determined, to evaluate the intercellular spaces of the epithelium. Rhodamine B was used as a lipophilic marker of transcellular permeability. Permeabilities of the excised rabbit corneas were determined in side-by-side diffusion chambers. RESULTS: The TER values of the corneal epithelial cultures were 200 to 800 Omega x cm(2), depending on the culture conditions. In optimal conditions, cultured corneal epithelium consisted of five to eight cell layers, TER was at least 400 Omega x cm(2), and the most apical cells were flat, with tight junctions, microvilli, and desmosomes. The permeability coefficients (P(cell), 10(-6) cm/sec) for (3)H-mannitol, 6-carboxyfluorescein, and rhodamine B were 1.42 +/- 0.36, 0.77 +/- 0.40, and 16.3 +/- 4.0, respectively. Corresponding values (at 10(-6) cm/sec) for the isolated rabbit corneas were 0.38 +/- 0.16, 0.46 +/- 0.27, and 18.1 +/- 4.0, respectively. CONCLUSIONS: The TER, morphology, and permeability of the cultured corneal epithelial cells resemble those of the intact cornea. This cell culture model may be useful in evaluation of corneal drug permeation and its mechanisms.

Psychosomatic disorder: a treatment problem more difficult than neurosis? A comparative clinical study of psychosomatic and neurotic patients of the psychiatric policlinic of a general hospital.

Two patient groups from the psychiatric policlinic of a general hospital were compared, the first comprised 93 patients with severe psychosomatic disorders who were not diagnosed as neurotic, and the second, 133 neurotic patients without psychosomatic symptoms. The aim of the study was to clarify anamnestic and personality differences between the groups and investigate their treatment motivation. The psychosomatic patients showed less motivation for psychiatric treatment, even though their psychiatric impairment was more severe than that of the neurotics and although the extent of their psychological symptoms was equally great. Compared with the neurotic patients, the ability to tolerate stress was poorer and the attitude toward the interview and the interviewer was more defensive in the psychosomatic patients. Compared with the neurotics, medical services were utilized to a greater extent by the psychosomatic patients, and their childhood environment and background development were characterized by somewhat more psychological disturbance.